Bronchiolization of the alveoli in lung cancer: pathology, patterns of differentiation and oncogene expression.
We examined the incidence and association of bronchiolization of the alveoli with non-small cell lung cancer in lung resection specimens from 2 patient groups: those with non-small cell lung cancer and those diagnosed with a variety of non-neoplastic lung conditions. We observed marked variation in bronchiolization of the alveoli morphology ranging from normal to severely atypical and developed a classification scheme based on growth pattern, cell number and cytologic criteria. Patterns of differentiation, proliferation and growth factor receptor and oncogene expression were studied using immuno-histochemical and in situ hybridization techniques. While low-grade (0-I) bronchiolization of the alveoli lesions demonstrated markers similar to normal bronchiolar epithelium, a significant decrease in the Clara cell 10 kDa protein and tubulin and an increase in surfactant protein-A expression were observed in high-grade (II-III) lesions. Focal p53 expression was detected in 2 high-grade lesions, while c-myc mRNA and cJun protein were observed in all grades. No correlation was observed between bronchiolization of the alveoli incidence and histologic tumor type. A comparison of marker expression in lesions and tumors from the same case revealed a negative correlation between cytokeratin-14 and c-erbB-2 immuno-reactivity. Only one bronchialization of the alveoli lesion was found in the non-neoplastic patient group. We conclude that up to 12% of non-small cell lung cancer resection specimens contain bronchiolization of the alveoli lesions which exhibit altered morphology and patterns of differentiation.
Jensen-Taubman
S M
SM
Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.
Steinberg
S M
SM
Linnoila
R I
RI
D001980:Bronchi / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002454:Cell Differentiation; D006801:Humans; D007124:Immunoenzyme Techniques; D007633:Keratins / Q000378:metabolism; D008171:Lung Diseases / Q000473:pathology*; D008175:Lung Neoplasms / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D014598:Uteroglobin
D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D011510:Proteolipids; D011518:Proto-Oncogene Proteins; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D017978:Receptors, Growth Factor; C556389:SCGB1A1 protein, human; D007633:Keratins; D014598:Uteroglobin